Lipedema is a chronic disease in adipose tissue affecting women. The distinctive body appearance in lipedema, often mistaken for obesity, may be detrimental to social life. In our online cross-sectional survey study, conducted from June to September 2021 among 245 women with lipedema, we found significantly more health-related stigma compared to an aged-matched general female population (N = 1872), leading to an overall lower quality of life. Conversely, strong social support was associated with better social and emotional functioning. As such, healthcare professionals must, even in the early stages, recognize this disease and address its impact on psychosocial health and well-being. Lipedema, which involves an abnormal accumulation of inflammatory body fat, mainly in the lower limbs, has a significant negative impact on physical health and social functioning (Dudek et al., Citation2021; Falck et al., Citation2022). Regretfully, lipedema is often misinterpreted as obesity, and diagnosis delays extend over decades (Torre et al., Citation2018). As such, many women must cope with their health problems independently (Falck et al., Citation2025; Melander et al., Citation2022). Owing to lipedema’s distinctive impact on body appearance and affected individuals’ futile attempts to lose weight, many women carry a heavy burden of self-blame and stigma (Dudek et al., Citation2018). Although the emotional impact of lipedema is significant, research from the affected women’s perspective is considerably sparse. In this study, we examined health-related stigma and social support and their relation to health-related quality of life (HRQoL) in a Swedish population of women with lipedema, intending to contribute to a broader understanding of the role of psychosocial factors when living with this chronic and burdensome disease.